TW201534354A - Adhesion preventing material - Google Patents

Abstract

The purpose of the present invention is to provide an adhesion preventing material which is designed so that the fluidity thereof changes with time in such a manner as being in the form of a gel with a high fluidity at administration and, after the administration to a surgical incision/suture site, being in the form of a gel with a low fluidity. A powdery adhesion preventing material to be mixed with an aqueous solvent before using, said adhesion preventing material containing alginic acid and/or a salt thereof and being designed so as to show a viscosity at 37 DEG C of 70 mPas.s or less 5 minutes after mixing with the aqueous solvent, and show a viscosity at 37 DEG C of 120 mPas.s or more 60 minutes after the mixing. When mixed with an aqueous solvent and administered at a clinical site, the adhesion preventing material is maintained in a highly fluid state at the administration and, after the administration to a surgical incision/suture site, the fluidity thereof is lowered to thereby achieve both excellent operability and excellent adhesion preventing effect.

Description

Adhesive Technical field

The present invention relates to a sticking prevention material which is in the form of a powder and which is used in combination with water at the time of use, and which is excellent in workability at a medical site and excellent in adhesion prevention effect of a living tissue.

Background technique

The term "sticking" refers to a state in which the original organs are close to each other, but the joints between the free organs or tissues are connected. Adhesion of the suture after surgery is a kind of artificial inflammatory adhesion, and even if there is a difference in degree, it is a high chance of complications due to surgery. Sticking to the absence of any symptoms does not pose a problem. However, since it may sometimes cause abdominal pain, ileus, infertility, etc., various measures have been taken so far in order to prevent sticking.

In the past, it was cut to prevent sticking by covering with a film, gel or the like. The method of suturing the part. In particular, the gel-like adhesion preventing material has a more easily adhered shape than the film shape and has been cut. The advantages of suturing the part and not easily peeling off, and simplifying the hand technique at the clinical site. In the past, as a gel-like adhesion preventing material, it was revealed that it contained seaweed. A polysaccharide such as an acid, a carboxylic acid group-containing compound, and a composition of water (see Patent Document 1).

If the operability of the clinical site is considered, the gel-like adhesion preventing material has been cut into the medicine. It is preferable that the portion to be sewn is highly fluid, however, it is preferable that the fluidity is low from the viewpoint of the adhesion preventing effect. Accordingly, the gel-like adhesion preventing material which has been conventionally disclosed is required to be gelled by mixing water with a gelling agent in advance, and has a fluidity opposite to that required for the adhesion prevention effect. Provided in a state of fluidity, it is not sufficient to satisfy both the operability and the adhesion prevention effect at the clinical site.

With such a prior art as a background, it is eager to develop a sticking prevention material which is designed to have a long-term change in fluidity so as to constitute a gelatinous substance with high fluidity when administered, and has been cut since being administered. The sutured portion constitutes a gel with a low fluidity.

Advanced technical literature Patent literature

[Patent Document 1] Japanese Patent Laid-Open Publication No. 2003-153999

Summary of invention

SUMMARY OF THE INVENTION An object of the present invention is to provide a sticking prevention material which is designed to have a change in fluidity over time, which exhibits a gel form which is highly fluid when administered, and which exhibits flow after administration to a portion which has been cut and sewn. Low concentration Gummy.

In order to solve the above problems, the inventors have found that a sticking preventive material is used in powder form and is mixed with an aqueous solvent at the time of use, and the sticking preventing material contains alginic acid and/or a salt thereof, and is It is mixed with an aqueous solvent so that the viscosity at 37 ° C is 70 mPas at a time point of 5 minutes after mixing with the aqueous solvent. Below s, at a time point of 60 minutes after mixing, the viscosity at 37 ° C is 120 mPas. s or more, if the adhesive material is mixed with an aqueous solvent when it is used in a clinical field, the fluidity is maintained at a high level when the drug is administered, and the fluidity is lowered after the drug is applied to the portion which has been cut and sewn, and the superiority can be achieved. The operability and adhesion prevention effect. The present invention has been completed based on the foregoing findings and by repeated review.

That is, the present invention provides the invention of the aspects disclosed below.

Item 1. A sticking preventing material characterized by being a powdery adhering preventing material which is used by mixing with an aqueous solvent, the sticking preventing material containing alginic acid and/or a salt thereof, and water-based The solvent is mixed and used so that the viscosity at 37 ° C is 70 mPas in the time point of 10 minutes after mixing with the aqueous solvent. s below, in the 60 minutes after mixing with the aqueous solvent, the viscosity at 37 ° C is 120 mPas. s above.

Item 2. The adhesion preventing material according to Item 1, which further comprises a salt of an organic acid and/or an inorganic acid and a divalent metal.

Item 3. The adhesion preventing material according to Item 1 or 2, which further contains polyethylene glycol.

Item 4. The adhesion preventing material according to any one of items 1 to 3, which further comprises an organic acid And / or its alkali metal salt.

Item 5. The adhesion preventing material according to Item 2, wherein the salt of the organic acid and/or the inorganic acid and the divalent metal is a calcium salt of an organic acid and/or an inorganic acid.

Item 6. The adhesion preventing material according to Item 4, wherein the organic acid and/or the alkali metal salt thereof is selected from the group consisting of alkali metal salts of gluconic acid-δ-lactone, gluconic acid and gluconic acid. At least one.

Item 7. The adhesion preventing material according to any one of Items 1 to 6, which is set to be mixed with an aqueous solvent at the time of use so that the alginic acid and/or its salt of the adhesion preventing material is 1 to 4% by weight.

Item 8. A gel-preventing gel-producing kit, which is constructed by accommodating the sticking preventing material according to any one of claims 1 to 7 in a syringe.

Item 9. A gel-preventing gel-making kit characterized in that it contains a powdery adhering preventive material and an aqueous solvent, and is mixed with a powdery adhering preventive material and an aqueous solvent at the time of use. In the case of preventing the adhesion of the gel, the powdery adhesion preventing material contains alginic acid and/or a salt thereof, and is set so as to mix the powdery adhesion preventing material and the aqueous solvent, 5 minutes after the mixing. At the time point, the viscosity of the adhesive gel at 37 ° C is prevented to be 70 mPas. s below, in the 60 minutes after mixing, the viscosity of the adhesive gel at 37 ° C is prevented to be 120 mPas. s above.

Item 10. The gel-preventing gel manufacturing kit according to Item 9, comprising: a syringe containing a powdery adhesion preventing material; and a container containing the aqueous solvent.

Item 11. The gel-preventing gel manufacturing kit of item 9, wherein In the container of the storage compartment which is separated by the separable partitioning mechanism, the powdery adhesion preventing material and the aqueous solvent are accommodated in the respective storage chambers in a separated state.

Item 12. A method for preventing sticking comprising the steps of: mixing the sticking preventive material according to any one of items 1 to 7 with an aqueous solvent, and applying to an affected part which must be prevented from sticking.

Item 13. Use of a powder containing alginic acid and/or a salt thereof for producing a powdery adhesion preventing material, wherein the powdery adhesion preventing material is mixed with an aqueous solvent to cause The viscosity at 37 ° C is 70 mPas at 5 minutes after mixing with the aqueous solvent. s below, in the 60 minutes after mixing with the aqueous solvent, the viscosity at 37 ° C is 120 mPas. s above.

The sticking preventing material of the present invention is provided in the form of a powder, and is mixed with an aqueous solvent at a clinical site during use, and is prepared to prevent sticking of the gel and to be applied to the incision and suture site where adhesion prevention is required. The anti-adhesive gel prepared by mixing the adhesion preventing material of the present invention with water is prepared into a gel having a high fluidity after being prepared for 5 minutes (mixed with an aqueous solvent), and therefore, is administered. The time point becomes a state in which it is easy to be administered to the incision and the suture site, and the operability at the clinical site is excellent. Further, the gel for preventing sticking which is obtained by mixing the sticking preventing material of the present invention with water can be a gel having a low fluidity at a time point after preparation (after mixing with an aqueous solvent) for 60 minutes, and therefore, It can be stably fixed at the incision and suture site of the administered medicine, and exerts an excellent adhesion prevention effect.

Further, in the adhesion preventing material of the present invention, in addition to alginic acid and/or a salt thereof, when combined, a salt containing an organic acid and/or an inorganic acid and a divalent metal, polyethylene glycol, an organic acid and/or In the case of the alkali metal salt, when it is mixed with an aqueous solvent, since a homogeneous gel can be prepared without agglomeration, it is easy to use at a clinical site without a stirring device for preparing a gel.

Further, since the adhesion preventing material of the present invention is provided and stored in a powder form, it is less susceptible to temperature and the like in a general storage state, and is also excellent in storage stability.

Further, by using the gel-preventing gel-producing kit of the present invention, it is possible to easily carry out the preparation of the adhesion-preventing gel by mixing the powdery adhering preventing material with water. In particular, if the gel-preventing gel-preventing kit is used in the syringe, the gel-preventing gel can be easily prepared, and the sticking can be easily performed. The gel is applied to the incision and the suture site, and the convenience of using the powdery adhesion preventing material can be improved.

1‧‧‧ nozzle

2‧‧‧Syringe body

3‧‧‧shims

4‧‧‧Plunger

5‧‧‧Applicator

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a view showing one aspect of a syringe used in the gel manufacturing kit of the present invention.

Fig. 2 is a graph showing the results of measurement of the viscosity of the gel for preventing adhesion when the water was used as the aqueous solvent in Test Example 1.

Fig. 3 is a graph showing the results of measurement of the viscosity of the gel for preventing adhesion by the use of physiological saline or lactated Ringer's solution as an aqueous solvent in Test Example 1.

Figure 4 is a graph showing the use of physiological saline or lactated Ringer's in Test Example 1. When the liquid is used as an aqueous solvent, the measurement of the viscosity of the gel for adhesion is measured.

Fig. 5 is a graph showing the results of measurement of the viscosity of the gel for preventing adhesion by the use of physiological saline or lactated Ringer's solution as an aqueous solvent in Test Example 1.

Fig. 6 is a graph showing the results of measurement of the movable region of the interphalangeal joint of the arthropod of each group in the test example 2 (the difference in the bending angle before and after the load).

Form for implementing the invention

The sticking preventive material of the present invention is used in combination with water in the form of a powder, and further contains alginic acid and/or a salt thereof, and is mixed with an aqueous solvent so as to be mixed for 5 minutes after being mixed with the aqueous solvent. The viscosity at 37 ° C is 70 mPas. s below, in the 60 minutes after mixing with the aqueous solvent, the viscosity at 37 ° C is 120 mPas. s above. Hereinafter, the adhesion preventing material of the present invention will be described in detail.

<viscosity characteristics>

The sticking preventing material of the present invention is in the form of a powder, and is mixed with an aqueous solvent at the time of use, thereby making it possible to use a gel for preventing sticking. In the present specification, the term "gel for preventing sticking" refers to a gelled product obtained by mixing the adhering preventing material of the present invention with an aqueous solvent.

Since the gel for preventing adhesion of the adhesion preventing material of the present invention is set to have high fluidity immediately after preparation, and fluidity is lowered after a predetermined period of time, excellent operability and adhesion prevention effect can be obtained. Both. Hereinafter, the viscosity characteristics of the adhesion preventing material of the present invention will be described.

When the adhesion preventing material of the present invention is mixed with a predetermined amount of an aqueous solvent, the viscosity increases with time. In the adhesion preventing material of the present invention, the viscosity of the adhesive gel at 37 ° C is prevented from becoming 70 mPas at a time point of 5 minutes after mixing with a predetermined amount of the aqueous solvent. s below. Accordingly, the viscosity is low and the fluidity is high until 5 minutes after mixing with the aqueous solvent, whereby the adhesion preventing gel can be easily administered to the incision and the suture site, and the incision can be easily and uniformly covered. The entire suture site is provided, and it has excellent operability at the clinical site.

If the operability of the clinical site is further improved, the viscosity at 37 ° C in the time point of mixing with the aqueous solvent should be, for example, 5 to 70 mPas. s. Especially if it is used in the field of plastic surgery, the viscosity is more preferably listed as 5~70mPas. s, and more preferably 10~60mPas. s, especially 15~50mPas. s. Moreover, if it is used in the field of digester, the viscosity is preferably listed as 20~70 mPas. s, and more preferably 30~70mPas. s, especially 50~70mPas. s.

Further, the adhesion preventing material of the present invention is set such that the viscosity at 37 ° C becomes 120 mPas at a time point of 60 minutes after mixing with a predetermined amount of the aqueous solvent. s above. According to this, at a time point of 60 minutes after mixing with the aqueous solvent, the viscosity is high and the fluidity is low, whereby the gel for preventing adhesion which has been administered to the incision and the suture site can be stably fixed and excellent. The adhesion prevents the effect.

From the standpoint of further improving the adhesion prevention effect, the viscosity at 37 ° C in the 60 minutes after mixing with the aqueous solvent is suitable for use in any of the fields of shaping and digester. List as 300mPas. Above s, and more preferably 1000mPas. s above. Further, the upper limit of the viscosity at 37 ° C in the 60 minute time after mixing with the aqueous solvent is not particularly limited, and for example, it may be, for example, 150,000 mPas. s.

Further, from the viewpoint of further enhancing the adhesion preventing effect, it is more desirable to have a viscosity in addition to the above range in the point of 5 minutes and 60 minutes after mixing with the aqueous solvent. After 30 minutes of solvent mixing, the viscosity of the adhesive gel at 37 ° C was prevented from 20,000 mPas. s below, and should be 10~10000mPas. s, more preferably 50~5000mPas. s.

Moreover, the viscosity-preventing material of the present invention may be set so that the viscosity in the time point of 5 minutes and 60 minutes after mixing with the aqueous solvent satisfies the above range. However, if the viscosity is satisfied, the drug can be prevented from being administered. Apply the gel to the incision. From the viewpoint of the fluidity at each corner of the suture portion and the excellent adhesion prevention effect of the gel for preventing adhesion by the incision and the suture portion, it is preferable to mix with the aqueous solvent. The viscosity at 37 ° C in the minute time point is usually 5 times or more at 37 ° C in the 60 minutes after mixing with the aqueous solvent, and preferably 10 times or more, more preferably 20 times or more. More than 50 times. Further, there is no particular limitation on the upper limit of the ratio of the viscosity in the time point of 60 minutes after the mixing at 37 ° C in the time point of mixing at 5 minutes after mixing with the aqueous solvent, for example, It is preferably 10,000 times or less, and preferably 5,000 times or less, more preferably 2500 times or less, and further preferably 1000 times or less.

Moreover, the adhesion preventing material of the present invention is only required to be dissolved in an aqueous solution. The viscosity in the 5 minute and 60 minute time points after the mixing of the agent satisfies the above range. However, the viewpoint of the fluidity of the gel for preventing adhesion before application and the adhesion preventing effect after administration can be more satisfactorily considered. In view of the above, it is preferred that the maximum rate of increase in viscosity is set to be 30 minutes after mixing with the aqueous solvent, and preferably 35 to 60 minutes, more preferably 45 to 60 minutes.

Further, in the present invention, the viscosity is measured by the following measurement conditions.

(1) In a glass test tube having a capacity of 10 ml, a predetermined mixing ratio is set, and the amount of the aqueous solvent is 5 mL, and a powdery adhesion preventing material and an aqueous solvent are added, and stirred by a vortex mixer for 20 seconds, and Modulate to prevent sticking of the gel. This operation was carried out at a temperature of 37 °C.

(2) After the completion of the stirring, the mixture was allowed to stand for 0 minutes, and the gel for preventing adhesion was allowed to stand at a temperature of 37 ° C, and the sample was sampled at a predetermined time, and the viscosity at 37 ° C was measured by the following measurement conditions.

Device: viscosity. Viscoelasticity measuring device (rheometer)

Temperature control unit: Peltier board

Measuring geometry: parallel plate with a diameter of 35 mm

Clearance: 1mm

Sample amount: 1mL

Stress applied: 11.90Pa

Frequency: 0.5000Hz

Angular velocity: 3.142rad/s

Moreover, the rate of increase of the viscosity is due to the aforementioned conditions. The viscosity was measured for a long time, and the value of the viscosity increase every 5 minutes was calculated from the mixing of the aqueous solvent.

The viscosity-preventing property of the gel for preventing sticking can be made by using alginic acid and/or a salt thereof as a gelling agent in the sticking preventing material of the present invention, and appropriately setting the content and other blending components, and appropriately The ground is set to have a mixing ratio with an aqueous solvent at the time of use.

<containing ingredients>

Alginic acid and/or its salt

The adhesion preventing material of the present invention contains alginic acid and/or a salt thereof (hereinafter, sometimes only indicated as component (A)) as a gelling agent.

The salt of the alginic acid is not particularly limited as long as it is pharmaceutically acceptable. Examples thereof include alkali metal salts such as sodium salts and potassium salts; and alkaline earth metal salts such as calcium salts.

The weight average molecular weight of the alginic acid and/or its salt is not particularly limited as long as it has the above-described viscosity characteristics. For example, it may be, for example, 50,000 to 600,000, and preferably 50,000 to 500,000, more preferably 8~ 500000.

Alginic acid and/or its salts are commercially available. For example, commercially available products of alginic acid and/or its salts can be exemplified by KIMICA ALGIN High. G series IL-6G (1w/v% aqueous solution, viscosity 50~80mPa.s at 20°C; weight average molecular weight about 680,000), I-1G (1w/v% aqueous solution, viscosity at 20 °C 100~200mPa. s; weight average molecular weight of about 720,000), I-3G (1w / v% aqueous solution, viscosity of 300 ~ 400mPa.s at 20 ° C; weight average molecular weight of about 800,000); KIMICA ALGIN I series IL-6 (1w / v% aqueous solution, viscosity at 20 ° C 50~80mPa.s; weight average molecular weight about 690,000), I-1 (1w / v% Aqueous solution, viscosity at 20 ° C 80 ~ 200mPa. s; weight average molecular weight of about 860,000), I-3 (1w / v% aqueous solution, viscosity of 300 ~ 400mPa.s at 20 ° C; weight average molecular weight of about 770,000), I-5 (1w / v% aqueous solution, 20 ° C viscosity 500 ~ 600 mPa.s; weight average molecular weight of about 800,000), I-8 (1w / v% aqueous solution, viscosity at 20 ° C 800 ~ 900mPa.s; weight average molecular weight of about 790,000), IL-1 (1w/v% aqueous solution, viscosity at 20 ° C 15mPa.s; weight average molecular weight of about 260,000), IL-2 (1w / v% aqueous solution, viscosity at 20 ° C 20 ~ 50mPa.s; weight average molecular weight of 580,000); KIMICA ALGIN ULV series ULV-5 (10w/v% aqueous solution, viscosity at 20 ° C 500~600mPa.s; 1w / v% aqueous solution, viscosity at 20 ° C 4mPa.s; weight average molecular weight of 80,000), ULV-10 (1w/v% aqueous solution, viscosity of about 7mPa.s at 20 °C; weight average molecular weight of about 90,000), ULV-20 (1w / v% aqueous solution, viscosity at 20 ° C 10mPa.s Left and right; weight average molecular weight of about 200,000), etc. (all made by KIMICA Co., Ltd.). Among these, preferred are, for example, I-1G, I-3G, I-1, IL-1, ULV-5, ULV-10, ULV-20, and the like.

The adhesion preventing material of the present invention may be selected from the group consisting of alginic acid and a salt thereof, and may be used alone or in combination of two or more. In the case of alginate and its salt, if it is further improved in the operability and adhesion prevention effect at the clinical site, it is preferable to enumerate, for example, alginic acid and an alkali metal salt thereof, and more preferably alginic acid. Sodium salt.

The content of the component (A) in the adhesion preventing material of the present invention may be appropriately set to have the above-described viscosity characteristics, and may be, for example, 1 to 50% by weight. If the viscosity characteristics are more appropriately provided and further The content of the component (A) is preferably 5 to 25% by weight from the viewpoint of improving the operability and the adhesion preventing effect at the clinical site.

Salt of organic acid and / or inorganic acid and divalent metal

In the adhesion preventing material of the present invention, a salt of an organic acid and/or an inorganic acid and a divalent metal (hereinafter sometimes referred to as a component (B)) may be contained. When the salt of the organic acid and/or the inorganic acid and the divalent metal is contained as described above, the viscosity characteristics described above can be satisfied, and both the operability and the adhesion preventing effect at the clinical site can be further improved.

The salt of the organic acid and/or the inorganic acid and the divalent metal used in the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, examples of the acid constituting the salt include organic acids such as gluconic acid, lactic acid, oxalic acid, citric acid, and acetic acid; and inorganic acids such as sulfuric acid, hydrochloric acid, phosphoric acid, and nitric acid. Further, examples of the divalent metal constituting the salt include barium, magnesium, calcium, iron, and the like. Among these divalent metals, calcium is preferable.

Specific examples of the salt of the organic acid and/or the inorganic acid and the divalent metal include calcium lactate, calcium gluconate, calcium sulfate, calcium citrate, calcium hydrogen phosphate (calcium monohydrogen phosphate, dihydrate), and the like. Among these, a salt which is poorly water-soluble is suitable from the viewpoint of having the viscosity characteristics in a more appropriate range. Specifically, the water-insoluble salt can be exemplified by calcium sulfate, calcium citrate, and monohydrogen phosphate. Dihydrate, calcium carbonate, and the like. In the present specification, the term "water insolubleness" corresponds to "not easily dissolved" to "almost undissolved" as defined in the 16th revised Japanese Pharmacy Law. In other words, it means a solvent for dissolving 1 g of a solute (a salt of an organic acid and/or a mineral acid and a divalent metal) and 100 mL or more.

The salt of the organic acid and/or the inorganic acid and the divalent metal is preferably, for example, calcium hydrogen phosphate or monobasic calcium phosphate. Dihydrate and calcium carbonate.

The organic acid and/or the inorganic acid and the divalent metal salt may be used singly or in combination of two or more kinds.

For example, the content of the organic acid and/or the inorganic acid and the divalent metal salt in the adhesion preventing material of the present invention may be, for example, 0.1 to 50% by weight, and preferably 1 to 20% by weight, more preferably 1 ~10% by weight.

In the adhesion preventing material of the present invention, the ratio of the component (A) to the component (B) is not particularly limited. However, the higher the ratio of the component (B) to the component (A), the gelation is exhibited. The faster the speed, the stronger the gel strength. Therefore, after considering these effects, it is appropriately set to have the above-described viscosity characteristics. For example, one part by weight of the average (A) component may be satisfied, and the component (B) may constitute a ratio of 1 part by weight or less. In particular, when the viscous property is provided in a more appropriate range and the operability and the adhesion preventing effect at the clinical site are further improved, for example, the average (A) component is 1 part by weight. The component (B) is preferably 0.01 to 1 part by weight, and more preferably 0.02 to 1 part by weight, particularly preferably 0.03 to 0.3 part by weight.

Polyethylene glycol

The adhesion preventing material of the present invention may contain polyethylene glycol (hereinafter, sometimes only indicated as component (C)). In the adhesion preventing material of the present invention, by containing polyethylene glycol together with the components (A) and (B), the viscosity characteristics can be satisfied, and when it is mixed with an aqueous solvent, it does not agglomerate and can be homogenized. Prevent sticking with gel.

The polyethylene glycol used in the present invention is preferably in a solid state at normal temperature. For example, the average molecular weight thereof may be, for example, 1,000 or more, and is preferably 3,000 or more. Specifically, for example, from about 1,000 to about 20,000, And it should be about 4000~about 20,000. When the average molecular weight of the polyethylene glycol is less than 1,000, the solid does not constitute a solid at normal temperature, and if the average molecular weight is more than 20,000, the viscosity is increased, so that it is difficult to handle at the time of production. Here, the average molecular weight of the polyethylene glycol is a value measured by the 16th corrected Japanese Pharmacopoeia method "polyethylene glycol 400" average molecular weight method.

Specifically, the polyethylene glycol may be, for example, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 1540, and polycondensate contained in the 16th revised Japanese Pharmacopoeia and pharmaceutical additives as raw materials for the production of materials. Ethylene glycol 3000, polyethylene glycol 3350, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, polyethylene glycol 20000, and the like. Among these, from the viewpoint of having the viscosity characteristics in a more appropriate range and further improving the operability and the adhesion preventing effect at the clinical site, it is preferable to exemplify: The alcohol 3350, polyethylene glycol 4000, polyethylene glycol 6000, and polyethylene glycol 20000 are more preferably exemplified by polyethylene glycol 3350 or polyethylene glycol 4000.

These polyethylene glycols may be used alone or in combination of two or more.

Further, in the adhesion preventing material of the present invention, the polyethylene glycol is preferably contained as a matrix substrate or a coating (coating) other component. When it is contained in the form of the substrate or the other component, the agglomeration when mixed with water can be more effectively suppressed, and the dissolution rate of the other components can be controlled by the dissolution rate of the polyethylene glycol itself. And more appropriate It has the aforementioned viscosity characteristics.

For example, the content of the component (C) in the adhesion preventing material of the present invention may be, for example, 1 to 99% by weight, and preferably 20 to 99% by weight, more preferably 50 to 80% by weight.

Organic acid and/or its alkali metal salt

Further, the adhesion preventing material of the present invention may contain an organic acid and/or an alkali metal salt thereof (hereinafter, it may be simply indicated as a component (D)). In the adhesion preventing material of the present invention, by containing an organic acid and/or an alkali metal salt thereof, the viscosity property can be provided in a more appropriate range, and the operability and adhesion prevention in the clinical field can be further improved. The effect is both.

The organic acid used in the present invention is not particularly limited, and examples thereof include glucono-δ-lactone, gluconic acid, glucuronic acid, galacturonic acid, oxalic acid, citric acid, acetic acid and the like. Further, as an example, the salt of the organic acid may, for example, be a sodium salt or a potassium salt. Among these, from the viewpoint of having the viscosity characteristics in a more appropriate range and further improving the operability and the adhesion preventing effect at the clinical site, it is preferable to enumerate, for example, gluconic acid-δ- An alkali metal salt of an ester, gluconic acid or gluconic acid, and more preferably sodium gluconate or glucono-δ-lactone. Further, glucono-δ-lactone is a compound which is hydrolyzed to gluconic acid upon contact with water and is acidic.

These organic acids and their alkali metal salts may be used alone or in combination of two or more.

For example, the content of the component (D) in the adhesion preventing material of the present invention may be, for example, 1 to 60% by weight, and preferably 2 to 50% by weight, more preferably 3 to 15% by weight. weight%.

Further, when the adhesion preventing material of the present invention contains the component (B) and the component (D), the blending ratio is not particularly limited. However, if the viscosity is contained in a more appropriate range, the viscosity is further improved. From the viewpoint of improving the operability and the adhesion preventing effect at the clinical site, for example, the component (D) is 0.01 to 80 parts by weight, and preferably 2 to 1 part by weight of the component (B). 50 parts by weight, more preferably 3 to 30 parts by weight.

Other mixed components

In addition to the above-mentioned components, the adhesion preventing material of the present invention may contain an antibacterial agent, an antibiotic agent, an anti-inflammatory agent, a bloodstream improving agent, a steroid agent, an enzyme inhibitor, or the like as needed for the purpose of promoting a therapeutic effect or preventing bacterial infection. Pharmacological components such as proliferation factors and various vitamins. Since the sticking preventing material of the present invention stays in the incision and suture portion to be applied for a certain period of time, by using the aforementioned pharmacological ingredient, it is also possible to use a medicine delivery system for the purpose of slow release of the pharmacological ingredient. .

Further, in the adhesion preventing material of the present invention, an additive such as an excipient, a binder, a lubricant, a pH adjuster, a buffer, a preservative, an antioxidant, a colorant, an anti-wetting agent, or the like may be contained as needed. .

Ideal combination of synthetic components

The adhesion preventing material of the present invention is limited to the above-mentioned (A) component, and the composition and the use state of the material are set to exhibit the viscosity characteristics, and the blending component other than the component (A) is not particularly limited. The combination of the desired blending components satisfying the above-mentioned viscosity characteristics may be, for example, a state containing the above components (A) to (C), and more preferably containing the above components (A) to (D).

shape

The particle size of the adhesion preventing material of the present invention is not particularly limited as long as it is in the form of a powder. However, from the viewpoint of improving the solubility when mixed with an aqueous solvent, for example, by sieve The particle diameter measured by the separation method may be, for example, about 200 to 2000 μm, and preferably about 355 to 1000 μm.

Modulation method

The adhesion preventing material of the present invention is prepared by mixing the above-mentioned (A) component and the above-mentioned (B) to (D) components and other pharmacological components or additives, and preparing the material into a powder form. Specifically, in the case where the adhesion preventing material of the present invention contains the component (C), preferred examples of the following preparation methods include the following methods.

In the first step, the component (C) is dissolved; and in the second step, the component (B) is added to the solution of the component (C) obtained in the first step, and the component (B) is added as needed. (D) a component and other pharmacological components or additives are mixed; and a third step of curing the mixture obtained in the second step and molding into a powder.

The dissolution of the component (C) in the first step can be carried out, for example, by a method of dissolving by heating or a method of dissolving in a solvent. When the component (C) is heated and dissolved, the temperature condition thereof can be appropriately set depending on the type of the component (C) to be used. For example, it is, for example, 50 to 90 ° C, and preferably 60 to 80 ° C. In addition, when the component (C) is dissolved in a solvent, for example, the component (C) can be mixed with a solvent such as an aqueous ethanol solution of 90 to 99% by volume to form 5 to 20% by weight. When the content of the component (C) in the pharmaceutical composition of the present invention is large (for example, When used as a medical material for preventing adhesion, the first step is preferably carried out by heating and dissolved, and when the content of the component (C) is small (for example, when used as a hemostatic agent), the first step It is preferably carried out by dissolution in a solvent.

When the component (C) is dissolved in a solvent in the first step, the solvent is removed during mixing or after mixing in the second step. The molding in the desired shape in the third step can be carried out by a known molding method such as pulverization or granulation.

Since the sticking preventive material of the present invention is applied to a living body, it is preferably used for sterilization. The sterilization method is not particularly limited, and examples thereof include, for example, EOG sterilization, electron beam sterilization, gamma ray sterilization, ultraviolet irradiation, etc., from the viewpoint of maintaining the stability of alginic acid and/or its salt, Preferred examples include electron beam sterilization, EOG sterilization, or gamma ray sterilization.

Use pattern

The adhesion preventing material of the present invention is provided in the form of a powder, and is mixed with an aqueous solvent at a clinical site during use, and is used as a gel for preventing adhesion.

The aqueous solvent to be used in the adhesion preventing material of the present invention is preferably a liquid solvent containing water as a solvent and is pharmaceutically acceptable, and is not particularly limited, and examples thereof include, for example, : purified water, physiological saline, Ringer's solution, lactated Ringer's solution, and the like. Among these, preferred ones are, for example, purified water.

The mixing ratio of the adhesion preventing material and the aqueous solvent of the present invention can be appropriately set to have the above-described viscosity characteristics. Specifically, the adhesion preventing material of the present invention can be mixed with an aqueous solvent to prevent the adhesion. In the gel, the concentration of the component (A) contained in the adhesion preventing material of the present invention is usually from 1 to 4% by weight, and preferably from 1 to 3% by weight. More specifically, when it is used in the field of plastic surgery, it is possible to set the adhesion preventing material of the invention to be mixed with the aqueous solvent to have a concentration of the component (A) of preferably 1 to 3% by weight, and more preferably 1.5 to 3 The weight %, in particular, is preferably 1.5 to 2.5% by weight, and if it is used in the field of the digester, the viscosity of the invention can be set to be mixed with the aqueous solvent to form the concentration of the above component (A). 4% by weight.

Further, when the adhesion preventing material of the present invention contains the component (A) to the component (C), or when the component (A) to the component (D) is contained, in order to have the viscosity characteristic, the invention can be set. The adhesion preventing material is mixed with an aqueous solvent to form a gel for preventing adhesion. The concentration of the adhesion preventing material of the present invention is usually 5 to 20% by weight, and preferably 5 to 15% by weight. More specifically, when the adhesion preventing material of the present invention contains the component (A) to the component (C), or when the component (A) to the component (D) is contained, the adhesion preventing material of the invention can be set. The mixture is mixed with an aqueous solvent, and if it is in the plastic field, the concentration of the adhesion preventing material of the present invention is preferably 5 to 15% by weight, and more preferably 6 to 15% by weight or 7.5 to 15% by weight, particularly preferably 6 ~12.5 wt% or 7.5~12.5 wt%; if it is in the field of digester, it should be 10-20 wt%, and more preferably 15-20 wt%.

The adhesion preventing material of the present invention is prepared by mixing with water to prepare a gel for preventing adhesion, and then applying the drug to an affected part (incision and suture site) which must be prevented from sticking. The gel for preventing sticking prepared by mixing the sticking preventing material of the present invention with an aqueous solvent exhibits a gel form having a high fluidity for 5 minutes after preparation (after mixing with an aqueous solvent), and therefore, it is preferable to Dosing within 5 minutes after preparation To the affected area. The method of administering the gel for preventing sticking prepared from the sticking preventing material of the present invention is not particularly limited, and for example, it can be applied to an affected part by a syringe, a bristles or the like.

The amount of the gel for preventing the sticking of the sticking preventing material of the present invention can be appropriately set according to the state of the affected part. For example, for example, it is required to prevent the sticking of the affected part every 1 cm ² , which prevents sticking The gel is composed of a range of 0.005 to 0.1 g.

Further, the body part to which the sticking preventing material of the present invention is applied is not limited to the extent that it is necessary to prevent sticking. For example, it may be in the field of the digestive part of the abdominal organ or the like, or may be The plastic surgery field of nerves, joints, etc. In particular, in the plastic surgery field such as sacs, nerves, joints, etc., the structure is fine, and if a conventional adhesion preventing material is used, it is difficult to apply to various corners of the tissue, however, if it is prepared by using the adhesion preventing material of the present invention, The gel for preventing sticking has a low viscosity at the time of administration and a high fluidity, and therefore has an advantage that it can be applied to each corner even in a portion having such a fine structure.

<Anti-adhesive gel manufacturing kit-1>

The adhesion preventing material is provided in a form that can be contained in a syringe and can be mixed with water in a syringe during use, whereby the adhesion preventing gel can be easily prepared at a clinical site. That is, the present invention provides a gel manufacturing kit configured to accommodate the adhesion preventing material in a syringe.

The syringe used in the gel manufacturing kit of the present invention is not particularly limited, and examples thereof include a syringe body having a nozzle at a distal end portion, and a gasket inserted into the syringe. The body is slidable in the axial direction of the syringe body; and a plunger that moves to operate the gasket. Further, the volume of the syringe body may be any size as long as it can accommodate the amount of the adhesion preventing gel corresponding to at least one administration amount, and examples thereof include 1 to 20 ml, and preferably 2 to 10 ml.

Further, the gel-producing kit of the present invention can be configured such that the adhesive-preventing material is accommodated in a syringe, and a predetermined amount of an aqueous solvent is inserted into the syringe during use to prepare a gel for preventing adhesion, and may be set to Two different regions are provided in the syringe, and the adhesion preventing material and the aqueous solvent are respectively stored in a predetermined amount in different regions, and can be mixed in the syringe during use. In the latter case, specifically, the adhesion preventing material chamber accommodating the adhesion preventing material and the aqueous solvent chamber accommodating the aqueous solvent may be contained in the syringe while being separated from each other, and the adhesive may be mixed during use. Prevent materials and aqueous solvents. A syringe which is designed to separate and provide two different regions and to mix the contents in the two regions during use is known, for example, from Japanese Laid-Open Patent Publication No. 2001-104482. Further, when the adhesion preventing material and the aqueous solvent are to be mixed in the syringe, the adhesion preventing material and the aqueous solvent may be brought into contact with each other in the syringe to be swung back and forth or left and right.

In the gel production kit of the present invention, the amount of the adhesion preventing material contained in the syringe may be an amount corresponding to at least one administration portion, and specifically, for example, 0.1 to 20 g or 0.1 to 2 g, And it should be 0.2~10g or 0.2~1g. In addition, when the adhesion preventing material and the aqueous solvent are accommodated in different regions in the syringe, the amount of the aqueous solvent contained in the syringe can be appropriately set in consideration of the mixing ratio of the adhesion preventing material and the aqueous solvent. Can meet the desired viscosity characteristics.

Further, in the gel manufacturing kit of the present invention, the applicator (tubular needle) for discharging the gel for preventing adhesion to the affected part may be attached to the nozzle at the tip end of the syringe body, or may be configured to be mounted Applicator. The applicator is not particularly limited as long as it can be used to prevent sticking of the adhesive in the syringe. However, it is preferably made of resin from the viewpoint of ease of administration to the affected part. Flexible material to form. Further, according to this, when the applicator is formed of a material made of resin and having elasticity, the shape thereof is not particularly limited, but it is desirable from the viewpoint of further improving the administration convenience to the affected part. It has a diameter of 0.1 to 5 mm and a length of 1 to 10 cm.

Figure 1 shows one aspect of a syringe used in the gel manufacturing kit of the present invention. The syringe shown in Fig. 1 is provided with a syringe body 2 having a nozzle 1 at a front end portion thereof, a gasket 3 inserted into the syringe body 2 and slidable in the axial direction of the syringe body, and a plunger 4 for moving operation thereof The gasket; further, an elastic resin applicator 5 is attached to the nozzle 1. The applicator 5 can also be provided in a state where it has been detached from the nozzle 1, and is used by being used in the nozzle 1.

<Anti-adhesive gel manufacturing kit-2>

Moreover, the present invention also provides a gel-preventing gel-preventing kit comprising the above-mentioned adhesion preventing material and an aqueous solvent, and mixing a powdery adhering preventing material and an aqueous solvent to prevent sticking. gel.

The composition of the adhesion preventing material and the aqueous solvent in the adhesion preventing gel manufacturing kit, the ratio of the adhesion preventing material to the aqueous solvent, and the like are as described above.

Further, the gel-preventing gel-producing kit is not limited in any case where the adhesive-preventing material and the aqueous solvent are supplied in a non-mixed state, and the sticky-preventing material and the aqueous solvent are mixed and used in use, and are not particularly limited. Specifically, for example, a state in which the adhering preventive material accommodated in the syringe and the aqueous solvent contained in the container different from the syringe are contained (the first example) is included; In the container of the storage compartment in which the partitioning mechanism is partitioned, the adhesion preventing material and the aqueous solvent are accommodated in the respective storage chambers (the aspect 2).

The construction of the syringe used in the foregoing Example 1 is as described above.

Further, the container used in the second aspect of the invention may be any container which is designed to have two storage chambers which are separated by a separable partitioning mechanism, and which are pressed, bent, etc. during use. The external force connects the two storage chambers. The construction of such a container is well known, and the shape of a trap cage, the shape of a small glass bottle, and the like are known. Specifically, a container having a shape of a trap is disclosed in Japanese Laid-Open Patent Publication No. Hei-4-364851, and the like. Moreover, it is also known to form a container having a small glass bottle shape and to connect the shape of a small glass bottle-shaped container to each other by using a double-ended needle disclosed in Japanese Laid-Open Patent Publication No. Hei 10-277133. Since the container of the shape of the trapping cage and the container of the shape of a small glass bottle can accommodate 0.1 to 20 g of the adhesion preventing material, and preferably 0.2 to 10 g, it is suitable for the case where the amount of the container cannot be stored in a syringe or the like. Adhesion preventive agent. Further, in the second aspect of the invention, since the adhesion preventing material and the aqueous solvent are supplied in advance in one container, the sample can be easily adjusted at the clinical site. There are also advantages in the prevention of adhesion to gels.

Example

Hereinafter, the present invention will be described in detail based on examples and the like, however, the present invention is not limited thereto.

Test Example 1. Evaluation of viscosity characteristics

Adhesion prevention

Sodium alginate and calcium hydrogen phosphate have been added to polyethylene glycol 4000 (manufactured by Sanyo Chemical Industry Co., Ltd.) which is melted at about 70 °C. Dihydrate (manufactured by Wako Pure Chemical Industries, Ltd.) and glucono-δ-lactone (manufactured by Spectrum Chenmical Mfg. Corp. USP) were thoroughly mixed with a stir bar and then naturally cooled. Then, the mixture was pulverized and sieved through a sieve of No. 22 (mesh hole 710 μm) of the Japanese Pharmacopoeia, and a powdery adhering preventive material which had passed through the sieve was obtained. The blending amounts of the respective components are shown in Table 1 below.

In the table, the content of each of the blended components is % by weight.

Sodium alginate is 90% by weight of KIMICA ALGIN ULV series ULV-5 (10w/v% aqueous solution, viscosity 500-600mPa.s at 20°C; manufactured by Himec) and KIMICA ALGIN I series I-1 (1w /v% water Solution, viscosity at 20 ° C 80 ~ 200mPa. s, a weight average molecular weight of about 860,000; a mixture of 10 parts by weight of a system made by Himec.

Viscosity measurement after mixing with water

The viscosity change after mixing with the purified water was measured for each of the adhesion preventing materials prepared as described above. Specifically, a concentration of 10 ml of purified water was added to a test tube having a capacity of 10 ml, and each of the adhesion preventing materials was added to form a concentration shown in Table 2, and stirred by a vortex mixer for 20 seconds, and prepared to prevent sticking. Glue (prescription 1~6). After the completion of the stirring, the mixture was allowed to stand for 0 minutes, and the adhesion preventing gel was allowed to stand at a temperature of 37 ° C for 60 minutes, and the viscosity at 37 ° C was measured for a long time by the following measurement conditions. In addition, all the operations in this measurement were carried out at a temperature of 37 °C.

Device: viscosity. Viscoelasticity measuring device (rheometer)

Temperature control unit: Peltier board

Measuring geometry: parallel plate with a diameter of 35 mm

Clearance: 1mm

Sample amount: 1mL

Stress applied: 11.90Pa

Frequency: 0.5000Hz

Angular velocity: 3.142rad/s

The results obtained are shown in Table 2, Figures 2 and 3. 2 and 3 are shown by changing the scale of the vertical axis (viscosity) for the same test result. In addition, in this test, it was confirmed that the adhesion preventing material of any of them was excellent in solubility in purified water, and even if it was mixed with purified water, it did not agglomerate and formed a homogeneous gel.

Further, it was confirmed that the gel for preventing adhesion prepared by the prescriptions 2 to 5 is suitable for discharge from the syringe at a time point of 5 minutes after preparation, and has fluidity for spreading to various corners of the application site. Further, it was confirmed that the gel for preventing adhesion prepared by the prescriptions 2 to 5 was formed into a gel form having a low fluidity which was easily fixed at the application site at a time point of 60 minutes after the preparation.

Viscosity measurement after mixing with physiological saline or lactated Ringer's solution

The viscosity change after mixing with physiological saline or lactated Ringer's solution was measured for each of the adhesion preventing materials prepared as described above. Specifically, a test tube having a capacity of 10 ml in 5 ml of a physiological saline solution or a lactated Ringer's solution (Lactec Injection manufactured by Otsuka Pharmaceutical Co., Ltd.) was added, and each of the adhesion preventing materials was added to form the concentration shown in Table 3. Stir using a vortex mixer for 20 seconds and prepare a gel to prevent sticking (Prescription 7~10). After the completion of the stirring, the mixture was allowed to stand for 0 minutes, and the adhesion preventing gel was allowed to stand at a temperature of 37 ° C for 60 minutes, and the viscosity at 37 ° C was measured under the measurement conditions as described above. In addition, all the operations in this measurement were carried out at a temperature of 37 °C.

The results obtained are shown in Tables 3, 4 and 5. Figures 4 and 5 show the scale of the vertical axis (viscosity) for the same test result. In addition, in this test, it is also confirmed that the solubility of any of the adhesion preventing materials in physiological saline or lactated Ringer's solution is good, and even if mixed with physiological saline or lactated Ringer's solution, It does not agglomerate and forms a homogeneous gel.

Further, it was confirmed that the gel for preventing adhesion prepared by the prescriptions 7 to 10 is suitable for discharge from the syringe at a time point of 5 minutes after preparation, and has fluidity for spreading to various corners of the application site. Further, it was confirmed that the gel for preventing adhesion prepared by the prescriptions 7 to 10 formed a gel having a low fluidity which is easy to be fixed at the application site at a time point of 60 minutes after the preparation.

Test Example 2. 腱 adhesion prevention effect

Male rats (Crlj: WI) (obtained from Charles River, Japan) were used, and the adhesion prevention effect of cockroaches was evaluated. Specifically, first, the membranous tendon sheath at the base of the rat's foot was longitudinally cut, and the deep toe flexor tendon was exposed and cut in half, thereby producing a sputum-injured model rat. On the other hand, in the purified water, the adhesion preventing material having the composition shown in Table 1 was added to constitute 2.5% by weight (prescription 1), 5% by weight (prescription 2), 10% by weight (prescription 4), and 15% by weight (prescription 4). Prescription 5) and 25% by weight (prescription 6), and fully shake to prepare a gel for preventing sticking, and apply 50 μL of the gel for preventing adhesion to the sputum damage model within 1 minute from the end of stirring. The rat has been cut in half and its surroundings. In addition, in order to prevent the sciatic nerve from being broken due to the movement of the rat itself, the sciatic nerve was cut and the animal was incubated for 4 weeks under the condition of restricting the automatic movement. After 4 weeks, the foot was cut from the ankle in a state in which only the long toe flexor of each rat was attached. The long toe flexor of the cut foot was loaded with a load of 60 g, and the angle of the toe joint (MTP) and the proximal interphalangeal joint (PIP) of the second toe before and after the load was measured. The difference in bending angle before and after the load was calculated according to the following formula. Further, for comparison, the same applies to the case where the physiological saline solution was administered instead of the gel for preventing adhesion.

[Equation 1] The difference in flexion angle before and after the load (°) = (the angle of the MTP after the load + the angle of the PIP after the load) - (the angle of the MTP before the load + the angle of the PIP before the load)

The results obtained are shown in Figure 6. From this result, it was confirmed that when the adhesion preventing gel of the adhesion preventing material of the present invention was produced by administration, the movable area of the interphalangeal joint was enlarged, and the adhesion after surgery was effectively suppressed. Also It is understood that the adhesion preventing gel prepared by mixing the adhesion preventing material in the purified water to form 5 to 15% by weight can exhibit an excellent adhesion preventing effect.

Test Example 3. Peritoneum-cecal adhesion prevention effect

Male rats (Crlj: WI) (obtained from Japan Charles River Co., Ltd.) were used, and the adhesion prevention effect of the side wall and the cecum was evaluated. Specifically, first, a 1×4 cm muscle strip of the right peritoneal abdominal oblique muscle and the internal oblique muscle of the rat was excised, and a side wall was produced. Next, it is rubbed through the side walls by gauze. Further, the cecum was taken out from the rat, and the entire area was wiped by gauze, and then allowed to stand at room temperature for 20 minutes while being exposed to the air. Then, the cecum was washed by a physiological saline solution (manufactured by Otsuka Pharmaceutical Factory Co., Ltd.). On the other hand, in the purified water, the adhesion preventing material having the composition shown in Table 1 was added to form 15% by weight (Prescription 5), and the gel for preventing adhesion was prepared by shaking sufficiently, and the stirring end time was started. The drug was administered within 1 minute to coat the entire area of the aforementioned cecal after washing. Next, the cecum which has been treated by the foregoing is placed in the side wall portion and returned to the abdominal cavity, and the abdomen is closed, and it is bred for 1 week. Open the abdomen after 1 week and observe the adhesion of the side wall to the cecum. The sticking state is based on the criteria shown below, and the sticking point score and the sticking degree score are obtained, and the total scores are calculated as the total sticking score. In addition, in this test, as a test, the test was carried out in the same manner as in the case of administering physiological saline to replace the gel for adhesion.

<sticky part score>

Score: status

0: no stickiness

1: Visible only on the incision of the side wall.

2: Viscosity is seen in both the incision portion of the side wall and the side wall.

<stickiness score>

Score: status

1: Mildly sticky; can be easily peeled off by sticky fingers.

2: moderately sticky; must be bluntly peeled off, peelable and sticky.

3: Severely viscous; must be peeled off sharply, and it can not be peeled off without any tissue disorder.

The results obtained are shown in Table 4. From this result, it was confirmed that the adhesion preventing gel obtained by using the adhesion preventing material can also exert an excellent adhesion preventing effect in the field of the digester.

Claims (13)

A sticking prevention material characterized by being a powdery adhesion preventing material and used in combination with an aqueous solvent in use, the adhesion preventing material containing alginic acid and/or a salt thereof, and being mixed with an aqueous solvent So that the viscosity at 37 ° C is 70 mPas in the point of 5 minutes after mixing with the aqueous solvent. s below, in the 60 minutes after mixing with the aqueous solvent, the viscosity at 37 ° C is 120 mPas. s above. The adherend preventing material of claim 1, which further contains a salt of an organic acid and/or a mineral acid and a divalent metal. The adhesion preventing material of claim 1 or 2 further contains polyethylene glycol. The adhesion preventing material according to any one of claims 1 to 3, which further contains an organic acid and/or an alkali metal salt thereof. The adhesion preventing material according to claim 2, wherein the salt of the organic acid and/or the inorganic acid and the divalent metal is a calcium salt of an organic acid and/or an inorganic acid. The adhesion preventing material according to claim 4, wherein the organic acid and/or an alkali metal salt thereof is at least one selected from the group consisting of alkali metal salts of gluconic acid-δ-lactone, gluconic acid, and gluconic acid. Kind. The adhesion preventing material according to any one of claims 1 to 6, which is set to be mixed with an aqueous solvent at the time of use so that the alginic acid and/or its salt of the adhesion preventing material is 1 to 4% by weight. A gel-preventing gel-forming kit is constructed by accommodating the sticking preventing material according to any one of claims 1 to 7 in a syringe. A gel-preventing gel-making kit characterized in that it contains a powdery adhesion preventing material and an aqueous solvent, and is mixed with a powdery adhering preventing material and an aqueous solvent to prevent sticking. In the gel, the powdery adhesion preventing material contains alginic acid and/or a salt thereof, and is set to a powdery adhesion preventing material and an aqueous solvent, at a time point of 5 minutes after mixing. To prevent the viscosity of the adhesive gel at 37 ° C is 70mPas. s below, in the 60 minutes after mixing, the viscosity of the adhesive gel at 37 ° C is prevented to be 120 mPas. s above. The gel-preventing gel-producing kit according to claim 9, comprising: a syringe containing a powdery adhesion preventing material; and a container containing the aqueous solvent. The gel-preventing gel-producing kit of claim 9, wherein the powdery adhering preventive material and the aqueous solvent are separated in a container having two storage compartments separated by a connectable partitioning mechanism It is stored in each storage room. A method for preventing sticking, comprising the steps of: mixing the sticking preventive material according to any one of claims 1 to 7 with an aqueous solvent, and applying to an affected part which must be prevented from sticking. A use of a powder containing alginic acid and/or a salt thereof for producing a powdery adhesion preventing material, which is mixed with an aqueous solvent to be mixed with an aqueous solvent In the last 5 minutes, the viscosity at 37 ° C is 70 mPas. Below s, at a time point of 60 minutes after mixing with an aqueous solvent, the viscosity at 37 ° C is 120mPas. s above.